MicroRNA‑19a‑3p inhibits the cellular proliferation and invasion of non‑small cell lung cancer by downregulating UBAP2L Retraction in /10.3892/etm.2022.11557

Pan,Yuejiang; Jin,Ke; Xie,Xuan; Wang,Kexi; Zhang,Huizhong

doi:10.3892/etm.2020.8926

MicroRNA‑19a‑3p inhibits the cellular proliferation and invasion of non‑small cell lung cancer by downregulating UBAP2L

Retraction in: /10.3892/etm.2022.11557

Authors:
- Yuejiang Pan
- Ke Jin
- Xuan Xie
- Kexi Wang
- Huizhong Zhang
View Affiliations

Affiliations: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China
Published online on: June 24, 2020 https://doi.org/10.3892/etm.2020.8926
Pages: 2252-2261

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

MicroRNAs (miRNAs) are increasingly recognized as important regulators of non‑small cell lung cancer (NSCLC) progression by directly regulating their target genes. The aim of the present study was to assess the biological role of miR‑19a‑3p in NSCLC. It was revealed that miR‑19a‑3p expression was significantly downregulated in human NSCLC tissues and cell lines compared with normal tissues and lung epithelial cells. In addition, a lower miR‑19a‑3p expression was significantly associated with Tumor Node Metastasis stage and lymph node metastasis. Furthermore, the upregulation of miR‑19a‑3p in NSCLC cell lines significantly inhibited cell proliferation, migration and invasion, as determined using an MTT, colony formation, wound healing and transwell Matrigel invasion assays, respectively. A luciferase reporter assay and western blotting determined that ubiquitin associated protein 2 like (UBAP2L) was a direct target of miR‑19a‑3p and could be inhibited through the upregulation of miR‑19a‑3p in NSCLC. In addition, UBAP2L silencing induced similar effects to those observed following miR‑19a‑3p overexpression. The overexpression of UBAP2L partially reversed the effects of miR‑19a‑3p on NSCLC cell lines. Collectively, these data indicated that miR‑19a‑3p may serve as a tumor suppressor partly through the regulation of UBAP2L expression in NSCLC and that the targeting of miR‑19a‑3p may be a novel method for NSCLC treatment.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016.PubMed/NCBI View Article : Google Scholar
2	Oser MG, Niederst MJ, Sequist LV and Engelman JA: Transformation from non-small-cell lung cancer to small-cell lung cancer: Molecular drivers and cells of origin. Lancet Oncol. 16:e165–e172. 2015.PubMed/NCBI View Article : Google Scholar
3	Peters S, Adjei AA, Gridelli C, Reck M, Kerr K and Felip E: ESMO Guidelines Working Group. Metastatic non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 23 (Suppl 7):vii56–vii64. 2012.PubMed/NCBI View Article : Google Scholar
4	Osarogiagbon RU, Lin CC, Smeltzer MP and Jemal A: Prevalence, prognostic implications, and survival modulators of incompletely resected non-small cell lung cancer in the U.S. national cancer data base. J Thorac Oncol. 11:e5–16. 2016.PubMed/NCBI View Article : Google Scholar
5	Zinner R, Visseren-Grul C, Spigel DR and Obasaju C: Pemetrexed clinical studies in performance status 2 patients with non-small cell lung cancer (Review). Int J Oncol. 48:13–27. 2016.PubMed/NCBI View Article : Google Scholar
6	Chargari C, Deutsch E, Le Pechoux C and Magne N: State of the art in chemoradiotherapy combinations and potential role in targeting therapy approaches in nonsmall cell lung cancer. Cancer Radiother. 13:114–122. 2009.PubMed/NCBI View Article : Google Scholar : (In French).
7	Hafner M, Landgraf P, Ludwig J, Rice A, Ojo T, Lin C, Holoch D, Lim C and Tuschl T: Identification of microRNAs and other small regulatory RNAs using cDNA library sequencing. Methods. 44:3–12. 2008.PubMed/NCBI View Article : Google Scholar
8	Pereira DM, Rodrigues PM, Borralho PM and Rodrigues CM: Delivering the promise of miRNA cancer therapeutics. Drug Discov Today. 18:282–289. 2013.PubMed/NCBI View Article : Google Scholar
9	Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S and Plasterk RH: MicroRNA expression in zebrafish embryonic development. Science. 309:310–311. 2005.PubMed/NCBI View Article : Google Scholar
10	Dar AA, Majid S, de Semir D, Nosrati M, Bezrookove V and Kashani-Sabet M: miRNA-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1 protein. J Biol Chem. 286:16606–16614. 2011.PubMed/NCBI View Article : Google Scholar
11	Ambros V: MicroRNA pathways in flies and worms: Growth, death, fat, stress, and timing. Cell. 113:673–676. 2003.PubMed/NCBI View Article : Google Scholar
12	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005.PubMed/NCBI View Article : Google Scholar
13	Wa Q, Li L, Lin H, Peng X, Ren D, Huang Y, He P and Huang S: Downregulation of miR19a3p promotes invasion, migration and bone metastasis via activating TGFbeta signaling in prostate cancer. Oncol Rep. 39:81–90. 2018.PubMed/NCBI View Article : Google Scholar
14	Zhang X, Chen Y, Zhao P, Zang L, Zhang Z and Wang X: MicroRNA-19a functions as an oncogene by regulating PTEN/AKT/pAKT pathway in myeloma. Leuk Lymphoma. 58:932–940. 2017.PubMed/NCBI View Article : Google Scholar
15	Maeda M, Hasegawa H, Sugiyama M, Hyodo T, Ito S, Chen D, Asano E, Masuda A, Hasegawa Y, Hamaguchi M and Senga T: Arginine methylation of ubiquitin-associated protein 2-like is required for the accurate distribution of chromosomes. FASEB J. 30:312–323. 2016.PubMed/NCBI View Article : Google Scholar
16	Li D and Huang Y: Knockdown of ubiquitin associated protein 2-like inhibits the growth and migration of prostate cancer cells. Oncol Rep. 32:1578–1584. 2014.PubMed/NCBI View Article : Google Scholar
17	Zhao B, Zong G, Xie Y, Li J, Wang H and Bian E: Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA inhibits human glioma cell growth in vitro. Int J Mol Med. 36:1012–1018. 2015.PubMed/NCBI View Article : Google Scholar
18	Ye T, Xu J, Du L, Mo W, Liang Y and Xia J: Downregulation of UBAP2L inhibits the epithelial-mesenchymal transition via SNAIL1 regulation in hepatocellular carcinoma cells. Cell Physiol Biochem. 41:1584–1595. 2017.PubMed/NCBI View Article : Google Scholar
19	He J, Chen Y, Cai L, Li Z and Guo X: UBAP2L silencing inhibits cell proliferation and G2/M phase transition in breast cancer. Breast Cancer. 25:224–232. 2018.PubMed/NCBI View Article : Google Scholar
20	Chai R, Yu X, Tu S and Zheng B: Depletion of UBA protein 2-like protein inhibits growth and induces apoptosis of human colorectal carcinoma cells. Tumour Biol. 37:13225–13235. 2016.PubMed/NCBI View Article : Google Scholar
21	Aucagne R, Girard S, Mayotte N, Lehnertz B, Lopes-Paciencia S, Gendron P, Boucher G, Chagraoui J and Sauvageau G: UBAP2L is amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis. FASEB J. 31:5012–5018. 2017.PubMed/NCBI View Article : Google Scholar
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
23	Wang L, Jiang CF, Li DM, Ge X, Shi ZM, Li CY, Liu X, Yin Y, Zhen L, Liu LZ and Jiang BH: MicroRNA-497 inhibits tumor growth and increases chemosensitivity to 5-fluorouracil treatment by targeting KSR1. Oncotarget. 7:2660–2671. 2016.PubMed/NCBI View Article : Google Scholar
24	Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, Cheng CL, Yu CJ, Lee YC, Chen HS, et al: MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 13:48–57. 2008.PubMed/NCBI View Article : Google Scholar
25	Yang J, Zhang Z, Chen C, Liu Y, Si Q, Chuang TH, Li N, Gomez-Cabrero A, Reisfeld RA, Xiang R and Luo Y: MicroRNA-19a-3p inhibits breast cancer progression and metastasis by inducing macrophage polarization through downregulated expression of Fra-1 proto-oncogene. Oncogene. 33:3014–3023. 2014.PubMed/NCBI View Article : Google Scholar
26	Fan L, Sha J, Teng J, Li D, Wang C, Xia Q, Chen H, Su B and Qi H: Evaluation of serum paired MicroRNA ratios for differential diagnosis of Non-Small cell lung cancer and benign pulmonary diseases. Mol Diagn Ther. 22:493–502. 2018.PubMed/NCBI View Article : Google Scholar
27	Heerboth S, Housman G, Leary M, Longacre M, Byler S, Lapinska K, Willbanks A and Sarkar S: EMT and tumor metastasis. Clin Transl Med. 4(6)2015.PubMed/NCBI View Article : Google Scholar